Projects per year
Abstract
© 2016 The Author(s)
The regulation of mitochondrial RNA processing and its importance for ribosome biogenesis and energy metabolism are not clear. We generated conditional knockout mice of the endoribonuclease component of the RNase P complex, MRPP3, and report that it is essential for life and that heart and skeletal-muscle-specific knockout leads to severe cardiomyopathy, indicating that its activity is non-redundant. Transcriptome-wide parallel analyses of RNA ends (PARE) and RNA-seq enabled us to identify that in vivo 5' tRNA cleavage precedes 3' tRNA processing, and this is required for the correct biogenesis of the mitochondrial ribosomal subunits. We identify that mitoribosomal biogenesis proceeds co-transcriptionally because large mitoribosomal proteins can form a subcomplex on an unprocessed RNA containing the 16S rRNA. Taken together, our data show that RNA processing links transcription to translation via assembly of the mitoribosome.
The regulation of mitochondrial RNA processing and its importance for ribosome biogenesis and energy metabolism are not clear. We generated conditional knockout mice of the endoribonuclease component of the RNase P complex, MRPP3, and report that it is essential for life and that heart and skeletal-muscle-specific knockout leads to severe cardiomyopathy, indicating that its activity is non-redundant. Transcriptome-wide parallel analyses of RNA ends (PARE) and RNA-seq enabled us to identify that in vivo 5' tRNA cleavage precedes 3' tRNA processing, and this is required for the correct biogenesis of the mitochondrial ribosomal subunits. We identify that mitoribosomal biogenesis proceeds co-transcriptionally because large mitoribosomal proteins can form a subcomplex on an unprocessed RNA containing the 16S rRNA. Taken together, our data show that RNA processing links transcription to translation via assembly of the mitoribosome.
Original language | English |
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Pages (from-to) | 1874-1890 |
Number of pages | 17 |
Journal | Cell Reports |
Volume | 16 |
Issue number | 7 |
Early online date | 4 Aug 2016 |
DOIs | |
Publication status | Published - 16 Aug 2016 |
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Dive into the research topics of 'Hierarchical RNA Processing Is Required for Mitochondrial Ribosome Assembly'. Together they form a unique fingerprint.Projects
- 6 Finished
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NHMRC Research Fellowships - Aleksandra Filipovska
Filipovska, A. (Investigator 01)
NHMRC National Health and Medical Research Council
1/01/14 → 31/12/18
Project: Research
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Enginered Proteins as Treatments for Mitochondrial Disease
Rackham, O. (Investigator 01) & Filipovska, A. (Investigator 02)
NHMRC National Health and Medical Research Council
1/01/13 → 31/12/15
Project: Research
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The Structure & Organization of the Mitochondrial Genome in Health & Mitochondrial Disease
Filipovska, A. (Investigator 01) & Rackham, O. (Investigator 02)
NHMRC National Health and Medical Research Council
1/01/13 → 31/12/16
Project: Research